Yan Su, Duan Bingfang, Li Yuanhao, Zhu Hongquan, Shi Zhaoqi, Zhang Xiaoxiao, Qin Yuanyuan, Zhu Wenzhen
Department of Radiology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China.
Clinical & Technical Solutions Philips Healthcare Beijing China.
Neuroimage Clin. 2025;45:103740. doi: 10.1016/j.nicl.2025.103740. Epub 2025 Jan 27.
Emerging insights into the pathophysiology of Parkinson's disease (PD) underscore the involvement of dysregulated neurotransmission, iron accumulation and oxidative stress. Nonetheless, the excitatory and inhibitory neurometabolites, the antioxidant glutathione (GSH), and magnetic susceptibility are seldom studied together in the clinical PD literature.
We acquired MEGA-PRESS and multi-echo gradient echo sequences from 60 PD patients and 47 healthy controls (HCs). Magnetic resonance spectroscopy voxels were respectively positioned in the midbrain to quantify neurotransmitter including γ-aminobutyric acid (GABA) and glutamate plus glutamine, and in the left striatum to estimate GSH levels. Group differences in metabolite levels normalized to total creatine (Cr) and their clinical relevance were determined. Furthermore, relationships among GSH levels, neurotransmitter estimates and susceptibility values were explored in both PD patients and HCs.
PD patients exhibited reduced midbrain GABA levels (P = 0.034, P = 0.136), diminished GSH in the left striatum (P = 0.032, P = 0.096), and increased susceptibility values in the substantia nigra (P < 0.001). Mesencephalic choline levels were correlated with the severity of rapid eye movement sleep behavior disorders symptoms, whereas striatal N-acetylaspartate levels were linked to Hoehn-Yahr stage and motor symptom severity. Notably, the disruption of associations between striatal GSH levels and susceptibility values in globus pallidus, as well as midbrain GABA levels, were evident in PD.
These findings offer compelling evidence for metabolic dysregulation in PD, characterized by a concomitant reduction in GABA and GSH levels, alongside iron deposition.
对帕金森病（PD）病理生理学的新见解强调了神经传递失调、铁积累和氧化应激的参与。然而，在临床PD文献中，兴奋性和抑制性神经代谢物、抗氧化剂谷胱甘肽（GSH）和磁化率很少一起研究。
我们从60名PD患者和47名健康对照（HCs）中获取了MEGA-PRESS和多回波梯度回波序列。磁共振波谱体素分别位于中脑以量化神经递质，包括γ-氨基丁酸（GABA）和谷氨酸加谷氨酰胺，并位于左纹状体以估计GSH水平。确定代谢物水平相对于总肌酸（Cr）的组间差异及其临床相关性。此外，还探讨了PD患者和HCs中GSH水平、神经递质估计值和磁化率值之间的关系。
PD患者中脑GABA水平降低（P = 0.034，P = 0.136），左纹状体GSH减少（P = 0.032，P = 0.096），黑质磁化率值增加（P < 0.001）。中脑胆碱水平与快速眼动睡眠行为障碍症状的严重程度相关，而纹状体N-乙酰天门冬氨酸水平与Hoehn-Yahr分期和运动症状严重程度相关。值得注意的是，在PD中，纹状体GSH水平与苍白球磁化率值以及中脑GABA水平之间的关联中断是明显的。
这些发现为PD中的代谢失调提供了有力证据，其特征是GABA和GSH水平同时降低以及铁沉积。
